McCulloch created The Venture Bros. storyline sometime prior to 2000.[citation needed] After working for the television program Sheep in the Big City and the live-action version of The Tick, McCulloch set to turning The Venture Bros. into an animated series. The Venture Bros. was originally conceived as a comic book story for an issue of Monkeysuit. McCulloch realized that his notes were too extensive for a short comics story and proposed that Comedy Central air The Venture Bros. as an animated series, but the network rejected it. Although the first draft of the pilot script was written in the spring of 2000, the premise was not greenlit until around the summer of 2002 by Adult Swim. McCulloch had not previously considered Cartoon Network because he "didn't want to tone The Venture Bros. down" and was unaware of the existence of the network's Adult Swim sub-unit.

With the revised pilot, production began in autumn of that year and the pilot was first run on February 16, 2003. The first season of the series was completed in 2004 and it was added to the summer schedule in August.[6]

Dr. Thaddeus "Rusty" Venture (voiced by James Urbaniak) a former boy adventurer and inspiration for the "Rusty Venture" cartoon series, runs what remains of Venture Industries, a once-leading global corporation established by his super-scientist adventurer father Jonas. Since Jonas' death, Venture industries has declined to a shadow of its former glory, now occupying only a portion of the vast and deteriorating Venture compound and external locations including a base on Spider Skull Island and the space station Gargantua-1, all built by Jonas. Dr. Venture follows in his father's footsteps by becoming a super-scientist himself, although his competence falls short of his father's and he frequently demonstrates questionable ethics, leading others to claim that his feeble successes merely capitalize on the work of his late father.

Brock Samson (voiced by Patrick Warburton) is the muscular, hyper-masculine bodyguard to the Venture family. Appointed by the Office of Secret Intelligence, Brock frequently uses his license to kill to protect the Venture family. Brock's response to any threat is sudden and brutal violence, and he is a ruthless (and somewhat sadistic) hand-to-hand combatant, usually preferring to use his favorite combat knife, his hands and feet, or his vintage Dodge Charger rather than firearms; the Monarch refers to him fearfully as Venture's "Swedish murder machine" ("Dia de Los Dangerous!"). Brock's enemy and love interest is the deadly Russian assassin, Molotov Cocktease.

In the fourth season, Brock Samson is replaced as bodyguard by Sergeant Hatred, a former supervillain and "cured" pedophile; his pedophilia is actually controlled by an experimental drug ("Nomolestol") given to him by the OSI and its effectiveness varies wildly between episodes.

Dr. Venture's deceased father, Dr. Jonas Venture (voiced by Paul Boocock), was the model super-scientist of his day. He was a visionary who changed the world with his inventions, and stands as the inspiration for most other protagonists in the series. He formed "Team Venture", a collection of friends and associates that helped him fight crime and subsequently save his son (Dr. Venture) from his arch-enemies. To help his son cope without a mother figure, he developed a loyal and rather emotional robot named H.E.L.P.eR. (listed in episode credits as voiced by "Soul-Bot") that accompanies and assists the Ventures.

Throughout the series, the Venture family has had various recurring antagonists. Many are current or former members of The Guild of Calamitous Intent, an organization originally founded to save mankind from self-destruction but which now serves as an ad hoc placement agency matching super villains with appropriate heroic nemeses. The organization is run by the mysterious leader known only as "The Sovereign", who is revealed to be real-life rock star David Bowie in episode 26.

The Venture Family's primary nemesis is the pernicious but ineffective super-villain the Monarch (voiced by Christopher McCulloch). Assuming the motif of a monarch butterfly and "arching" Dr. Venture since college, the Monarch will stop at nothing to kill Dr. Venture (even though his motive is unknown). Accompanying the Monarch is the masculine-voiced Dr. Girlfriend, (voiced by Doc Hammer) referred to by the Monarch as "Dr. Mrs. The Monarch" after their wedding.

Baron Werner Ünterbheit (voiced by T. Ryder Smith) is a former dictator of the duchy of Ünterland and bears a grudge against Venture. He blames Venture for the loss of his jaw in college, citing, "One is always supposed to look out for one's lab partner!" The season-three premiere reveals that the Monarch was responsible for the explosion, an attempt on the life of Dr. Venture.

Phantom Limb (voiced by James Urbaniak) is a ruthless killer, villain insurance agent, and high-ranking Guild member (or was until he tried to usurp David Bowie as the Sovereign). Also, he was the former lover of Dr. Girlfriend before she left him to become The Monarch's companion.

The second season of the series premiered on the internet via Adult Swim Fix on June 23, 2006 and on television on June 25, 2006; the season finished on October 15, 2006. The considerable delay between the end of the first season and the start of the second was partially caused by Adult Swim's delay in deciding whether to renew the show, primarily because the show is drawn and inked in the traditional animation style (albeit digitally), causing each episode to take considerable time to move through production. Additionally, the producers were dealing with the time constraints of producing a first-season DVD that contained live action interviews and commentary for several episodes.

The third season began on June 1, 2008 and marked the beginning of the show's broadcast in high-definition. A 15-minute rough cut of "The Doctor Is Sin" aired on April 1, 2008 as part of Adult Swim's April Fool's Day theme of airing sneak peeks of new episodes.

The fourth season was split into two segments airing a year apart, with the first eight episodes airing in the Fall of 2009 and the remaining episodes in Fall of 2010.[7]

A note contained in the closing credits of the Season 4 finale indicated that the series would continue into a fifth season. jackson publick announced on his live Journal in 2011, that the show had been renewed for Seasons 5 and 6.[8] Season 5 began airing June 2nd, 2013.

Since the first season, two credits have changed every episode. Soul-bot's "voicing" the character H.E.L.P.eR., and another as a nickname for animation director Kimson Albert. Each nickname is a quote from its respective episode. In season two, each end credit sequence holds a different additional, fake duty for AstroBase Go!.[9]

Since season 2 the premiere episode of every season has its own distinct opening credit sequence, usually replacing the running silhouettes of Hank & Dean Venture with the characters central to the episode's story.

One of the themes of The Venture Bros. is its multifarious use of allusion in its dialogue, character design and other facets. The series openly pays homage to a variety of sources, including adventure serials, pulp magazines, David Bowie, Klaus Nomi, Hunter S. Thompson and many other elements of pop culture; musical references, television shows, theater, movies, toys, fads, and comic books have all been used for fodder.

The series' predominant homage is to Jonny Quest, as it is the basis for many of the main characters. Dr. Venture is modeled after what a child such as Jonny Quest might have grown up to be like after having lived through a childhood filled with bizarre, life-threatening events. Brock is modeled on Race Bannon. The Venture boys parody the Hardy Boys and take the places of Jonny and Hadji. However, the original Jonny Quest characters also make appearances on the show. In the episode "Ice Station – Impossible!", Brock mentions that he had served with Race Bannon on several occasions. He regards his fellow agent with respect calling him "one of the best."

Dr. Venture is a washed up, pill-popping super-scientist who treats his children and those around him with overt disdain and contempt; Brock is their hyper-aggresive bodyguard with a (frequently used) license to kill and a love for Led Zeppelin; and the boys are two pie-eyed teens stuck in an out-of-date mindset. One newspaper critic remarked, "If filmmakers Woody Allen and Sam Peckinpah had collaborated on Jonny Quest, it would have come out a lot like this."[10] In season 2, Jonny Quest was introduced into the show as Action Jonny, a homeless drug addict who deeply resents his father. As of season 4, Jonny is somewhat stable, and in a support group for former-boy adventurers, along with Dr. Venture, the first Wonder Boy, RoBoy, and The Hale Brothers–the final three being parodies of Robin, Astro Boy, and The Hardy Boys respectively.

In the commentary for the episode "Home Insecurity", Hammer and Publick elaborated on the theme.

Publick: "This show... If you'll permit me to get 'big picture', this show is actually all about failure. Even in the design, everything is supposed to be kinda the death of the space-age dream world. The death of the jet-age promises."

Hammer: "It's about the beauty of failure. It's about that failure happens to all of us...Every character is not only flawed, but sucks at what they do, and is beautiful at it and Jackson and I suck at what we do, and we try to be beautiful at it, and failure is how you get by...It shows that failure's funny, and it's beautiful and it's life, and it's okay, and it's all we can write because we are big...failures. (laughter)"[11]

This two disc set includes all 13 episodes of Season 1. The episodes are presented as broadcast, with bleeped profanity. Bonus features include "The Terrible Secret of Turtle Bay" (the pilot) and "A Very Venture Christmas", deleted scenes, behind the scenes mockumentary with the Venture Bros. Cast and creators commentaries on "Mid-Life Chrysalis", "Eeney, Meeney, Miney... Magic!", "Tag Sale – You're It!", "Ghosts of the Sargasso", "Return to Spider-Skull Island", and "The Terrible Secret of Turtle Bay".

Season Two

April 17, 2007

13

This two disc set includes all 13 episodes of Season 2. As with the Season 1 DVD release, any nudity has been covered with black bars and the profanity has been censored. Bonus features include commentary on every episode by Jackson Publick and Doc Hammer and, for some episodes, "special guests" such as voice actors James Urbaniak and Michael Sinterniklaas. Features also include deleted scenes and a tour of Astro-base Go!.

Season Three

March 24, 2009

13

This two disc set includes all 13 episodes of Season 3. Unlike the previous DVD releases, Season 3 is uncensored, with all profanity and nudity intact. Bonus features include deleted scenes and commentary. The season was also released on Blu-ray, which is packaged with a soundtrack CD that includes 20 tracks comprising the score from the season.[12] The box cover is based on the box covers of many video games on the Atari 2600. Although the Blu-ray is only available in the "Region A" zone, it functions in the "Region B" zone also.

Season Four, Volume One

October 26, 2010

8

This one disc DVD set includes the first 8 episodes of Season 4. Similar to the Season 3 set, all episodes are uncensored. Bonus features include deleted scenes and commentary.[13] Both halves of Season 4 will be released on the Season 4 Blu-Ray.

Season Four, Volume Two

March 22, 2011

8

This one disc DVD set includes the final 8 episodes of Season 4. Similar to the Season 3 set, all episodes are uncensored. Bonus features include deleted scenes and commentary.[14] Both halves of Season 4 will be released on the Season 4 Blu-Ray, to be released on the same day.

The first season of The Venture Bros. on DVD was released on May 30, 2006, as officially announced by Warner Home Video.[15] It coincided with the June 25 premiere of the second season. Originally, it was scheduled for March 14, 2006, but was delayed until May 30, 2006. The DVD packaging and interior art was created by comic artist [wikipedia:Bill Sienkiewicz|[Bill Sienkiewicz]]. On May 31, 2006, the season one DVD reached #1 on Amazon's top selling DVDs list.[16]

On March 27, 2010, series creator Jackson Publick revealed on his Livejournal that a standard definition DVD of the first half of season 4 would likely be released some time between July and October 2010, with a DVD of the second half of the season and a Blu-ray box set of the entire season to be released after the full season has aired. [17]

On a June 30, 2006, LiveJournal post, Jackson Publick revealed that he and Doc Hammer had recorded a commentary track for the season one episode "Home Insecurity". Warner Bros. chose to omit this track from the Season One DVD due to space limitations and some minor sound quality issues. Publick also stated that the commentary can be found and downloaded from Quickstop Entertainment.[18]

For the video release of the Season 3, a soundtrack album was also released, titled The Venture Bros.: The Music of JG Thirlwell. This is the same audio CD included as a bonus with the Blu-ray version of Season 3. While the CD release was originally made available at Adult Swim's website, it was given a wide release on May 12, 2009;[19] the vinyl LP release came out a month earlier. It can also be downloaded from most major digital retailers. The CD features 20 tracks, while the vinyl LP release is 16 tracks.[20]

In the episode "The Trial of the Monarch", The Monarch mentions a picture of Dr. Girlfriend "skinny dipping with Jim Foetus," a reference to Thirlwell.